Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide for agricultural, industrial, and domestic purposes. Previous studies have reported the adverse effects of CPF, such as intoxication incidents, endocrine disruption, cardiovascular diseases, as well as histopathological and oxidative damage. The aims of the present study were to elucidate short time subacute toxicity of CPF in male rats. Sprague-Dawley male rats (n = 32) were divided into four groups (n = 8) and received CPF as 3.25 mg/kg body weight (b.w) (Group A), 6.75 mg/kg b.w (Group B), 13.5 mg/kg b.w (Group C), and corn oil (control or Group D) daily via gavage for 15 days. The rats were sacrificed and oxidative damages, pro-inflammatory cytokines (TNF-α, IL-1β), and histopathological changes were determined in the lung, liver, kidney, heart, and testis tissues as well as plasma.According to our result, administration of CPF caused a significant increase in malondialdehid level and catalase activity while a significant decrease in superoxide dismutase activity in all tissues. In addition, a significant decrease in TNF-α observed in all tissues and plasma duo to the CPF. Histopathological evaluation of CPF-treated samples revealed a dose-dependent tissue toxicity in the liver, heart, lung, and kidney with less sensitivity of testicular and kidney tissues. These results suggest the potential of CPF in inducing oxidative stress at low doses and short duration time with similar trends in different tissues. As well as, due to the effects of CPF on some pro-inflammatory mediators, more comprehensive studies are recommended.