Approximately 20% of couples worldwide are infertile and about half of these couples have male infertility. Therefore, it is important to develop effective strategies for preventing male infertility. In this study, we examined the effects and regulatory mechanisms of curcumin, an active ingredient in the traditional herbal treatment derived from the dietary spice turmeric (Curcuma longa), on exogenous scrotal heat stress-induced testicular injuries in mice. Adult mice were orally administered three different doses of curcumin (20, 40, or 80 mg per kg per day) for 14 consecutive days and then subjected to transient scrotal heat stress at 43 °C for 20 min on day 7. The testes and blood of the mice were collected on day 14. Mice exposed to heat stress showed low testicular weight, severe vacuolization of seminiferous tubules followed by loss of spermatogenic cells, and the appearance of multinucleated giant cells and degenerative Leydig cells. In addition, great changes in oxidative stress (lipid peroxidation, superoxide dismutase (SOD) activity, cytoplasmic SOD, mitochondrial SOD, and phospholipid hydroperoxide glutathione peroxidase mRNAs), apoptosis (B-cell lymphoma-extra large and caspase 3 mRNAs), heat shock reaction (heat shock transcription factor-1 and transforming growth factor-β1 mRNAs) and androgen biosynthesis (testosterone concentration and 3β-hydroxysteroid dehydrogenase mRNA) were observed. However, all these testicular injuries induced by the scrotal hyperthermia were significantly improved by curcumin treatment (20, 40 and 80 mg kg(-1)) in a dose-dependent manner via its antioxidative, anti-apoptotic and androgen synthesis effects, indicating that it has the potential to prevent male infertility.