Objective The aim of the present study is to investigate the effect of benzene on the liver and kidney function and blood nucleotide level in Wistar rats. Methods The Wistar rats were treated with benzene (0.19, 0.38, 0.76 g/kg body weight) for 21 days. Different blood components were detected by an automatic biochemical analyzer. The blood cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and heat shock protein-70 (HSP-70) levels were determined by enzyme linked immunosorbent assay method (ELISA). Results When Wistar rats were administered with benzene at the of 0.19, 0.38, or 0.76 g/kg body weight for 21 days, the total serum bilirubin level was increased than the control group by 134.40%, 173.63% and 254.75%, respectively; aspertate aminotransferase (AST) was increased by 70.76%, 85.44% and 106.61%, creatinine was increased by 24.54%, 67.46% and 84.50%, creatine kinase was increased by 151.35%, 180.85% and 245.54%, urea (0.38 and 0.76 g/kg body weight groups) was increased by 0.48% and 23.43%; alanine transaminase level exceeded the upper limit of the readings, (1185.60%); cAMP level was increased by 41.84%, 264.02% and 314.23%, respectively, cGMP was increased by 31.29%, 40.46% and 272.14%, HSP-70 was increased by 82.11%, 187.37% and 1484.21%; amylase level was reduced by 62.03%, 63.66% and 62.03%, respectively, than the control group. Conclusion Our results demonstrate that benzene pollution affects the plasma cAMP and cGMP ratio, causing metabolic changes even structural damages in liver and kidney function.