Colorado potato beetle (CPB) (Leptinotarsa decemlineata Say) is an economically important pest of potato. The pest developed resistance to numerous insecticides with various modes of action, so it is necessary to explore the possibilities of using alternative, more environmentally acceptable insecticides and methods of control. A possible solution of these problems is the use of new groups of insecticides, such as biotechnical and biological insecticides, on which resistance has not yet been reported, and are at the same time more selective and ecologically acceptable. When combining insecticides with different modes of action, it is possible that the effect of the combination is not the sum of the action of the components in the mixture, but that it is the result of their interaction. Some interactions have a positive effect and others have a negative effect on the final effect on the harmful insect. Therefore, before applying a combination of insecticides in the field need to explore the interactions and determine the possible combined effect. Conducted laboratory research was aimed to determine the nature of the interactive relationship between spinosad and azadirachtin and spinetoram and azadirachtin measured as feeding capacity and mortality of larvae of CPB. The experiment was designed according to an internationally accepted method for the detection of resistant insects, IRAC-Method No. 7, Insecticide/Acaricide Suspectibility Test. Investigated combinations have shown satisfactory performance and, even in case of an independent synergism, can be recommended for use in integrated crop control programs of the potato from CPB. The experiment included 10 insecticide variants (single insecticides at different doses and combinations) and untreated control. The trial included 10 insecticide variants (single insecticides at different doses and combinations) and untreated control. A combination of low dose of azadirachtin (25 %) with a low dose of spinosad (5 %) have resulted with antagonism and it should not be used regardless of the environmental acceptability. Future research should determine the possibility of combining these active substances in different doses. A combination of low dose of azadirachtin (25 %) and low dose spinetoram (5 %) are suitable for use in integrated potato from CPB. The components in the combinations are significantly reduced in dosage, which means lower costs of suppression, while reducing environmental pollution and reducing the negative impact on natural balance. They also performed well in preserving the leaf area of the potatoes. The results of laboratory experiments should be verified in a field experiment. Proven ability to use more environmentally friendly insecticides contributes new strategies to control CPB.