This study was aimed at determining the acute and chronic toxic effects of cypermethrin, propetamphos, and combined cypermethrin and propetamphos. Four groups, each comprising 10 animals, were established for the acute (a) and chronic (b) toxicity trials, and in total, 80 male Wistar albino rats were used. In the acute toxicity trial, the first group was maintained for control purposes, and groups 2a, 3a, and 4a were administered only once with 80 mg/kg.bw of cypermethrin, 25 mg/kg.bw of propetamphos and 80 mg/kg.bw of cypermethrin combined with 25 mg/kg.bw of propetamphos, respectively, by gavage directly into the stomach. In the chronic toxicity trial, the first group was also maintained for control purposes, while groups 2b, 3b, and 4b were administered daily with 12 mg/kg.bw of cypermethrin, 4 mg/kg.bw of propetamphos, and 12 mg/kg.bw of cypermethrin combined with 4 mg/kg.bw of propetamphos respectively, by gavage directly into the stomach for 60 days. Blood and tissue (liver, kidney, brain, spleen, and testis) samples were taken 24 h after pesticide administration in the acute toxicity trial and at the end of day 60 in the chronic toxicity trial. Oxidative stress (MDA, NO, SOD, CAT, GSH-Px, and G6PD) parameters, serum biochemical parameters (glucose, triglyceride, cholesterol, HDL, LDL, BUN, creatinine, AST, ALT, ALP, protein, and albumin) and hepatic drug-metabolizing parameters (CYP2E1, CYPB5, CYTC, GST, and GSH) were investigated in the samples. When administered either alone or in combination, both pesticides inhibited the antioxidant enzymes and increased MDA and NO levels. For the drug-metabolizing parameters investigated, particularly in the chronic period, either increase (CYP2E1, CYPB5, and CYTC) or decrease (GST and GSH) was observed. Furthermore, some negative changes were detected in the serum biochemical parameters. In result, cypermethrin and propetamphos combinations and long-term exposure to these combinations produced a greater toxic effect than the administration of these insecticides alone. (C) 2015 Wiley Periodicals, Inc.