Objective <p>A genome-wide association study (GWAS) in the general Japanese male population suggested that the aldo–keto reductase family 1 member C3 (<i>AKR1C3</i>) gene was associated with sperm concentration. AKR1C3 is a metabolic enzyme in the testosterone synthesis pathway that may be involved in spermatogenesis. In this study, to determine the involvement of AKR1C3 in spermatogenesis, we examined the effects of AKR1C3 inhibitors and inducers on rat sperm count.</p> Methods <p>Indomethacin was used as an AKR1C3 inhibitor, and fenofibrate was used as an inducer. The rats were randomly divided into groups of nine, and indomethacin (1&#xa0;mg/kg/d) and fenofibrate (20&#xa0;mg/kg/d) were administered orally to 5-week-old male rats for 30&#xa0;d. The control group received a 0.5% sodium carboxymethylcellulose solution. Sperm counts were measured at the end of the treatment. They were also mated with female rats, and the litter size was determined.</p> Results <p>At the end of treatment, sperm counts tended to be lower in the indomethacin group than in the control group. In contrast, sperm counts were significantly higher in the fenofibrate group than in the control group (<i>p</i> = 0.018). Litter size after mating with female rats was significantly reduced in the indomethacin group compared to the controls (<i>p</i> = 0.016).</p> Conclusion <p>Indomethacin, an inhibitor of AKR1C3, tended to decrease sperm count in rats, suggesting that AKR1C3 affects spermatogenesis. Fenofibrate, an inducer of AKR1C3, significantly increased sperm count in rats. Fenofibrate is a potential treatment for male infertility.</p>