Investigation of probable toxic effects of acetamiprid (ACMP) on kidney and comparative analysis of the probable protective effects of vitamin E and melatonin were conducted in the present study. The ethics committee approval was obtained from Inonu University Medical Faculty Ethics Committee. Fifty Balb-c mice were randomly assigned to control, corn oil, ethyl alcohol, ACMP, ACMP + melatonin, ACMP + vitamin E, and ACMP + melatonin + vitamin E groups. At the end of the experiments, rat kidney tissues were incised under anesthesia. Blood samples and kidney tissues were examined. After 21 days of ACMP administration, it was observed that malondialdehyde (MDA), total oxidant status (TOS), BUN, creatinine, IL-6, IL-1 beta, and TNF-alpha levels, histopathological damage, and Caspase-3 immunoreactivity scores increased, and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) levels decreased, and histopathological damages were observed. Melatonin and vitamin E administration led to improvements in oxidative stress parameters, renal functions, inflammatory markers, and histopathological findings. ACMP administration led to nephrotoxicity in rat kidney tissues. Although melatonin and vitamin E administrations were effective on ACMP nephrotoxicity separately, co-administration of both was quite effective. Concomitant use of melatonin and vitamin E could be effective on prevention of toxicity.