In parallel with industrial advancements, number of the occupational diseases secondary to chemical exposure is increasing. The chemical agents in the work places affect various organ and tissue systems, leading to chronic diseases including infertility. Therefore, the aim of this study was to determine whether the exposure for paints and smoking can correlate with hormonal and trace element levels or not in order to determine their relationship and significance in male infertility. For these reasons, a hundred and fifty two male painters diagnosed with occupational diseases related to paints exposure in Damietta were included. In addition, forty of the healthy non-exposed and non-smoker males with the same age range to that of the painters were used as controls. The painters were classified into non-smokers and smokers. The non-smokers were either exposed for paints for less than 15 years (GII) or for more than 15 years (GIII) and the smoker painters were either exposed for less (GIV) or more than 15 years (GV). In sera of the non-smoker painters (GII and GIII) the mean levels of testosterone were lowered by 40.8% and 51.2% that of the smoker painters (GIV and GV) were reduced by 44.6% and 51.5%, respectively, than that of the control. On the other hand, the levels of estradiol (E2) in sera of all painters, groups were elevated than that of the control, especially in GIII and GV (97.1%, 138.2%, 117.8% and 147.6%, respectively). On the other hand, the mean levels of nitric oxide (NO) in sera of the same groups were 328.6%, 483.3%, 447.6% and 511.0% higher than that of the control group, respectively. In addition, the mean serum levels of cadmium (Cd2+) were elevated by 55.6%, 86.1%, 94.4%, and 119.4%, lead (Pb2+) by 90.4%, 379.5%, 495.9% and 653.4%, cobalt (Co2+) by 140.5%, 153.2%, 279.7% and 406.3%, nickel (Ni2+) by 23.3%, 33.3%, 113.3% and 123.3% and copper (Cu2+) by 14.6%, 22.0%, 26.8% and 63.4% in GII, GIII, GIV and GV, respectively. In conclusion, the results of this study illustrated that paints, exposure can participate in male infertility possibly via hormonal, heavy metals and nitric oxide-mediated mechanisms.