Doxorubicin (DOX) is a powerful chemotherapy agent associated with several harmful side effects including cardiovascular and skeletal muscle dysfunction. The observed muscle dysfunction can have a significant impact on the capacity of the DOX-treated patient to perform activities of daily living. Although it has been shown that aerobic and anaerobic exercise before treatment can minimize the degree of DOX-induced muscle dysfunction, few studies have examined the effect of resistance training (RT) on muscle dysfunction during chemotherapy treatment with DOX. PURPOSE: To examine the ability of RT on skeletal muscle dysfunction during DOX treatment using a rat model. METHODS: Male Sprague-Dawley rats (N=39) were randomly assigned to one of four groups: Sedentary + Saline (SS, n=8), Sedentary + DOX (SDOX, n=10), RT + Saline (RTS, n=12), and RT + DOX (RTDOX, n=9). Animals in the RT groups were housed in specialized cages where the food and water height was progressively elevated so that they achieved an erect bipedal stance to access their food and water for a total of 15 wk. Animals in the sedentary groups remained in standard animal housing for the duration of the study. Starting week 10, animals received weekly intraperitoneal injections of DOX (3 mg/kg) for 4 wk. One week after their last injection, animals underwent ex vivo muscle analysis of the soleus (SOL) and extensor digitorum longus (EDL) muscles. A one-way ANOVA with Tukey’s post-hoc testing was used to detect significance. RESULTS: Maximal twitch forces for the EDL were significantly lower in the SDOX (6.01 + 1.85 g/s vs. 11.39 + 3.48 g/s, p=≤0.05) group compared to SS. Rats in the RTDOX had a significantly higher maximal twitch force compared to SDOX (9.37 + 3.01 vs. 6.01 + 1.85 g/s, p=≤0.05) and a significantly lower twitch force compared to RTS (9.37+ 3.01 vs. 15.42 + 4.83, p=≤0.05) for the EDL. No significant differences were found among the groups for maximal twitch forces in the SOL. CONCLUSION: These findings suggest that DOX-induced muscle dysfunction is more pronounced in the EDL than the SOL. However, it appears that RT during treatment is effective in mitigating some of the effects of DOX-induced muscle dysfunction in the EDL.