Evidence from recent animal studies suggest that minocycline, a broad-spectrum antibiotic capable of regulating immune processes, may possess antidepressant properties. These studies, however, have yet to be comprehensively reviewed. Accordingly, this systematic review and meta-analysis summarizes the extant literature examining the effect of minocycline on depressive-like behavior in rodent models. PubMed, PsycINFO, and Web of Science databases were systematically searched for articles that met prespecified inclusion and exclusion criteria, and standardized mean differences (SMDs) were calculated for each continuous measure of depressive-like behavior. The overall effect of minocycline on depressive-like behavior was estimated using robust variance estimation meta-analysis. Separate subgroup analyses were conducted on diseased vs healthy animal models, different rodent species, and immobility-based vs anhedonia-based measures of depressive-like behavior. A total of 22 preclinical studies (816 animals) were included. Overall, minocycline reduced depressive-like behavior in rodents (SMD = -1.07, 95% CI -1.41--0.74, p < 0.001). Subgroup analyses revealed that minocycline reduced depressive-like behavior in diseased, but not healthy, animal models. Finally, minocycline was found to reduce both immobility-based and anhedonia-based outcomes. These findings suggest that minocycline may be an effective treatment of core depressive symptoms, and that further investigation of minocycline treatment for clinically relevant depression in humans is warranted.