Abstract: Background and Objective: Several studies indicate that pesticide intoxication produces oxidative stress. This oxidative stress plays an important role for human health and contributes significantly to many diseases and other chronic health effects. This study aimed to determine the role of oxidative stress of pesticides occupational exposure and smoking on male reproductive hormones and the antagonistic role of antioxidant enzymes. Materials and Methods: Follicle Stimulating Hormone (FSH), Luteinizing hormone (LH) and testosterone, Malondialdehyde (MDA), Superoxide dismutase (SOD), reduced glutathione (GSH), Glutathione S-transferase (GST) and Glutathione peroxidase (GPx), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were estimated in 51agriculture workers occupationally exposed to pesticides and 50 controls. Results: Results revealed significant decrease in AChE, BuChE, GSH and SOD levels in the workers compared to controls and significant increase in MDA, GPx and GST. Moreover, MDA and FSH were significantly increased among the smoker workers compared to non-smoker workers. The MDA was significantly correlated with GST and inversely correlated with AChE and BuChE in exposed workers. The FSH and LH were significantly correlated with SOD. Conclusion: Occupational exposures to pesticides and smoking have synergistic oxidative effect on FSH. It seemed that SOD and GST play important roles in antagonizing this oxidative stress among the examined pesticides workers. Therefore, smoking cessation and improving in the dietary habits with antioxidant supplementation could be essential for protection against the chronic toxic effects of occupational exposure to pesticides on the male reproductive hormones among smokers.