In this study, the characteristics of cocaine (COC) interaction with delta-9-tetrahydrocannabinol (THC) on glucose metabolism in the rat testis were investigated at different time points. Rats receiving 20 mg/kg IP COC at 0830 h and sacrificed at 15 min, 30 min and 60 min posttreatment showed no change in glucose metabolism. Moreover, 5 mg/kg, IV, COC treatment at 0900 h to rats and sacrificed 60 min postexposure, also produced no change in glucose metabolism. However, at 1300 h, the same protocol with IV COC treatment resulted in a significant increase in glucose utilization by the testis. Furthermore, a THC dose of 10 mg/kg, PO to the rats at 0830 or at 1130 h, followed by sacrifice 90 min later caused a significant decrease in glucose utilization at both time points. Similarly, when rats were given both THC and COC (THC at 0830 h, COC 90 min later) and sacrificed 60 min post-COC, it resulted in a further decrease in testicular glucose metabolism as compared to the rats treated by THC alone. On the other hand, concurrent exposure of rats to these drugs at 1300 h with same protocol, ended up with no change in glucose utilization in the testis. These data suggest that not only the route of administration but also the time of exposure plays an important role in defining the nature of the effects of COC/THC interaction on rat testicular glucose metabolism.