OBJECTIVES: A drug like Sildenafil is commonly used for the treatment of erectile dysfunction. Eruca sativa is known as a garden plant used in folk medicine to enhance the sexual desire in males. Nevertheless, the interaction of Sildenafil and Eruca sativa was not studied. In the current study, we aimed to examine the influence of Eruca sativa on Sildenafil pharmacokinetics in rats. STUDY DESIGN: A crossover experiment with washout period of two weeks was conducted. To one group of animals, Eruca sativa was given as food and a drinking solution to rats for 12 hours before the day of the experiment. On the day of the experiment, the same group received 5 ml (50 mg/ml) orally and a half an hour later animals received 1 ml Sildenafil citrate (2.85 mg/kg) oral administrated to the study group. The other group of rats only received Sildenafil. Two-weeks later a cross-over design on the same animals was conducted. Blood samples were collected from optical vein on different time intervals, samples were analyzed using validated (HPLC-UV) method. RESULTS AND CONCLUSION: Pre-administration of Eruca sativa has increased Sildenafil Cmax from 226.72 to 345.25 ng/ml, (p<0.05). In addition, the AUC of Sildenafil has significantly increased when it was pre-administered with Eruca sativa (550.59 vs. 916.48 ng/ml*hr). Our findings suggest that co-administration of Eruca sativa with Sildenafil enhances the pharmacokinetics of Sildenafil in rats plasma.