Background <p>Sex differences in inflammatory bowel disease (IBD) have been reported in humans, and gonadal steroid hormones are implicated in these sex differences. Although pain is a primary complaint among IBD patients, and pain often does not correlate with colon pathology, most animal studies focus on physiological rather than behavioral measures of IBD severity. Thus, the present study determined whether the impact of colitis on global measures of well-being is greater in female than male rats, and whether testosterone ameliorates this impact in females.</p> Methods <p>Blank capsules were implanted into gonadally intact adult females and males, and another group of females was implanted with testosterone-filled capsules. Three weeks later, trinitrobenzene sulphonic acid (TNBS) was administered intracolonically to induce colitis. Body weight and continuous, home cage wheel running were measured daily, before and for 10 days after colitis induction. Estrous cycle was monitored for 21 days in a subset of females. At the end of the study, serum testosterone and estradiol were determined, in addition to clitoral/preputial gland size.</p> Results <p>TNBS suppressed body weight and wheel running, which partially recovered within 10 days, with no group differences in magnitude or time course of these effects. Serum testosterone was elevated in testosterone-treated compared to control females and did not differ significantly from males, whereas serum estradiol was similar across groups. Testosterone suppressed females’ estrous cycling and increased clitoral gland size. At the end of the study, serum estradiol was found to be correlated with suppression of body weight and wheel running during the previous 10 days.</p> Conclusions <p>These results do not support the hypothesis of sex differences in well-being after IBD induction, or that testosterone ameliorates IBD effects in females, but corroborate human and rodent data suggesting that estradiol is associated with IBD severity in both sexes.</p>