Introduction. Osteoarthritis (OA) is the most common joint disease and among the most important causes of pain, disability and economic loss in all populations. A substantial fraction (12 %) of the overall burden of disease of OA arises secondary to joint trauma. With the best current care of significant joint injuries, the risk of post-traumatic OA (PTOA) ranges from about 20 % to more than 50 %. Considering that disease-modifying OA therapies are presently not available, and numerous positive effects of pentadecapeptide BPC 157 on healing of different injuries and tissues, the need for this investigation is imposed. Materials and methods. Research was conducted on surgical model of knee PTOA in the rat (female Wistar albino rats weighing an average of 200 g and aged 8-10 weeks, kept in standard conditions) after MCL transection, medial meniscectomy and ACL transection of the right knee. Pentadecapeptide BPC 157 was administred in doses of 10 μg/kg or 10 ng/kg, dissolved in drinking water, perorally (0,16 μg/ml or 0,16 ng/ml, 12 ml/rat/day, dailly till sacrifice), and dissolved in saline solution, intraarticularly (20 μg/ml or 20 ng/ml, 0,1 ml/aplication, two weeks interval, first aplication immediately after surgery, last aplication two weeks before sacrifice). Control groups received pure drinking water or 0,1 ml of saline solution intraarticularly. Considering route of administration and administred dose, after surgery animals were distributed in 12 treated and 6 control groups (each group with 5 animals), randomly (cotreatment 4 weeks, cotreatment 8 weeks, post-treatment 8 weeks - treatment started after 4 weeks). Throughout whole duration of experiment, functional measurements (gait analysis, extensor postural thrust, assessment test for knee contracture) were conducted on day 1, 7, 14, 28, 42 and 56 after surgery. Sacrifice was conducted on day 28 for cotreatment 4 weeks, and on day 56 for cotreatment 8 weeks and post-treatment. Immediately after sacrifice radiological interpretation and macroscopical assessment were conducted, as well as preparing of samples for histological interpretation. Results. Functional indicators in all control groups clearly indicated significant loss of function of operated leg immediately after surgery. As opposed to control groups, all cotreated groups showed substantially faster and more complete functional recovery. In post-treated groups contrary to control groups improvement of function was visible throughout time, however definitive values differed significantly from normal values. Macroscopical and histological, as well as radiological indicators in control groups showed clearly expressed signs of moderate PTOA after 4 weeks, and clearly expressed signs of heavily, advanced PTOA after 8 weeks. As opposed to control groups, all cotreated groups showed substantially better results. In post-treated groups in comparison with control groups differences were significantly lower. Effectiveness of pentadecapeptide BPC 157 is clearly visible at peroral and intraarticular administration, and at doses of 10 μg/kg and 10 ng/kg. Statistical analysis showed results statistically significant (P<0,05). Conclusion. Pentadecapeptide BPC 157 administration have substantial effect on prevention of developement and progression of PTOA, and on regression of already developed PTOA on surgical model of knee PTOA in the rat, independently of admistration route and administred dose.