Abstract: In order to screen out the chemical agents for controlling wheat leaf rust, pyraclostrobin, epoxiconazole and their combinations with different proportions were evaluated in this study, and the indoor control efficacies on wheat leaf rust as protective agents were determined by spray inoculation method, the safety on wheat and the field control efficacy of wheat leaf rust of the optimal compound ratio for indoor screening were investigated. The results showed that pyraclostrobin, epoxiconazole and their combination had strong inhibitory effect on the lesion expansion of wheat leaf rust. Among them, pyraclostrobin had stronger inhibitory activity, and its EC₅₀ value was 0.01 μg/mL. The results of joint toxicity evaluation showed that all combinations showed a synergistic additive efficacy, and the maximum synergistic coefficient was 1.50 with the mass ratio of pyraclostrobin-epoxiconazole as 50∶133. Both the indoor and field tests showed that the control efficacy was positively correlated with the established concentration gradient. In the field test with 120 a.i. g/hm², the control efficacy of pyraclostrobin + epoxiconazole 26% SC was 85.12%, which was better than that of single-agent treatments. The safety evaluation tests showed that all treatments could make different varieties of wheat grow normally without drug damage. This study had shown that the combination of pyraclostrobin and epoxiconazole had a good control efficacy on wheat leaf rust, providing a theoretical basis for the prevention and control of wheat leaf rust and scientific medication in production.