Background <p>Hypercholesterolemia and hyperglycemia are serious health problems that have been linked to low testosterone levels and testicular dysfunction. No previous studies have examined the protective effects of policosanol against testicular injury induced in rats by hypercholesterolemia and hyperglycemia. Therefore, this study aimed to investigate the protective effect of policosanol against testicular injury in hypercholesterolemic hyperglycemic rats, and to compare them to those of atorvastatin, a standard hypolipidemic drug.</p> Methods <p>Rats were assigned into normal and hypercholesterolemic hyperglycemic groups that received an STZ injection and a high cholesterol diet. The hypercholesterolemic hyperglycemic control group (HC-STZ) received no further treatment. The policosanol group received oral policosanol, daily for 8 weeks, while the atorvastatin group received oral atorvastatin, daily for 8 weeks.</p> Results <p>Both policosanol and atorvastatin increased testis weight and serum testosterone levels and improved the histological architecture of the testes. Their therapeutic effects in the testes were mediated via reducing oxidative stress, exerting an antiapoptotic effect, and improving the levels of enzymes responsible for testosterone synthesis.</p> Conclusion <p>Since policosanol showed similar therapeutic effects to those of atorvastatin, it may be a promising therapeutic approach against testicular injury in the context of hypercholesterolemia and diabetes.</p>