Abstract Rheumatoid arthritis (RA) is characterized by erosive pathology associated with joint inflammation and a sexual dimorphism with increased prevalence in females. Here we aim to determine whether androgen is protective against inflammatory-erosive disease in tumor necrosis factor-transgenic (TNF-Tg) mice. Wildtype (WT) and TNF-Tg male mice underwent sham (WT, n=3; TNF-Tg, n=7) or orchiectomy (WT, n=3; TNF-Tg, n=7) surgery at 1-month-old to remove androgen production confirmed by serum testosterone concentration. Cohorts of orchiectomized TNF-Tg males were treated with either 5ɑ-dihydrotestosterone (DHT; 0.025mg/day) (n=3) or placebo (n=3) via subcutaneous pellet insertion. Weekly clinical measures, along with mid-hindpaw bone volumes and ankle histology at 3-months-old were evaluated for all groups. Orchiectomies in TNF-Tg males significantly decreased serum testosterone (p<0.05), weight gain (p<0.001), and mid-hindpaw bone volumes (p<0.05) in comparison to sham TNF-Tg mice. The cuboid bone also had increased synovitis by histology with the loss of androgen (p<0.05). Treatment of orchiectomized TNF-Tg males with DHT protected against these changes in weight gain (p<0.01) and bone erosion (p<0.05) associated with decreased osteoclast number in the cuboid (p<0.01). In the TNF-Tg model of chronic inflammatory arthritis, androgen is protective in erosive disease. The loss of endogenous androgen significantly accelerated the progression of inflammatory-erosive arthritis in male TNF-Tg mice to a similar severity as age-matched female mice. In addition, treatment with exogenous androgen prevented this observed bone loss in orchiectomized TNF-Tg males. Overall, androgen delays and limits bone erosion even in the presence of active inflammation and future studies are warranted to elucidate the associated mechanisms.