In this study, the effect of pomegranate seed oil (PSO) on HCBD-induced nephrotoxicity was investigated in adult male rats. Animals were divided into five groups. Group 1 was treated with corn oil (1 mL/kg, i.p.). Group 2 received a single dose of HCBD (50 mg/kg, i.p.). Groups 3-5 were treated with PSO (0.16, 0.32, and 0.64 mg/kg, i.p., respectively) 1 h before HCBD (50 mg/kg, i.p.) injection. A significant elevation of serum creatinine and urea (p < 0.001) levels as well as urine glucose and protein (p < 0.001) concentrations (as markers of acute renal failure) was observed 24 h after administration of HCBD as compared to control group. HCBD also caused a significant decrease in total thiol content (p < 0.001) and a significant increase in thiobarbituric acid reactive species (TBARS, as an index of lipid peroxidation) levels (p < 0.001) in kidney homogenate samples. PSO pretreatment resulted in a significant and dose-dependent decrease in serum creatinine (p < 0.001) and urea levels (p < 0.001) as well as urine glucose (p < 0.001) and protein concentrations (p < 0.001) when compared with HCBD treated alone. PSO also significantly reversed the HCBD-induced depletion in total thiol content (p < 0.001) and elevation in TBARS (p < 0.001) in kidney homogenate samples. The results of this study showed that PSO clearly attenuated HCBD-induced nephrotoxicity, but explanation and mechanism of this protection need further explorations.