The aim of the thesis was to create an ex vivo model of the mammalian limb bud development for research of temperature changes and epigenetic drugs without the influence of the maternal organism. 13 and/or 14 days old limb buds were microsurgically isolated from Fisher rat embryos and cultured from 3 to 14 days in culture with serum (Eagle's MEM with 50% rat serum) or chemically defined media (MEM, or MEM with defined supplements) at normothermia (37 ºC), the two-week hypothermia (31 ºC) and hyperthermia (43 ºC, 15 min applied at the beginning of culture). The overall growth of ellipsoidal explants was measured with an ocular micrometer, and the calculated area (A) was standardized on the day of plating (A0). The numerical density (Nv) of the mmunohistochemically detected marker of cell proliferation (PCNA) was assessed. Part of explants was transplanted under the kidney capsule of anaesthetized males. A classical light microscopy and statistical analysis of the results was performed. Ex vivo experiments revealed the growth and progress of differentiation into cartilage, epidermis and myotubes, while grafts of explants previously cultured in serum at normothermia expressed the residual potential for ossification and differentiation of skin appendages and nerves. Overall growth, Nv PCNA and histomorphology in the two-week normothermia conditions were the best in controls with serum and most affected in pure MEM. On hyperthermia, significant negative impact on the overall growth in the three-day cultures with serum was discovered, but Nv PCNA was significantly higher in both the serum supplemented and MEM culture conditions. In the two-week hypothermia overall growth did not differ depending on the media, or of normothermia. However, Nv PCNA was significantly lower than in the control with serum at normothermia. Epigenetic drug 5-azacytidine in comparison to controls reduced the growth and differentiation at all temperatures except at two-week normothermia in MEM (5μM), where the growth of the front limb buds was even significantly higher. NvPCNA was significantly lower in MEM with serum under the influence of 5-azaC. In prolonged hypothermia in MEM, 5-azaC reduces Nv PCNA while at hyperthermia it caused Summary necrosis in the three-day culture with serum (30μM). Trichostatin A (33nM) in MEM increased overall growth at normothermia, but without the possibility of survival for 14 days and also decreased growth, Nv PCNA and differentiation (no myotubes) at hyperthermia. TSA reduced Nv PCNA in a three-day culture at hyperthermia. In the original model that was established specific influences of temperature changes and epigenetic drugs on the parameters of the limb development, especially on survival, overall growth, and proliferative potential were discovered. That is of importance for a better understanding of possible side-effects of combined physical and pharmacological therapy.