In cancer cachexia, erythropoietin often yields beneficial therapeutic effects by improving patient's metabolic and exercise capacity via an increased erythrocyte count. However, erythropoietin also has counter-regulatory effects against pro-inflammatory cytokines, which are postulated to be mediators of cancer cachexia. We investigated the mechanisms by which erythropoietin improves the cachectic condition. In this study, 100 Units/day of erythropoietin were administered intraperitoneally to BALB/c male mice, carrying a subclone of colon 26 adenocarcinoma, beginning on the day after tumor inoculation and continuing until they died. Erythropoietin administration attenuated the decline in body weight, as well as the decline in fat and muscle weights, of tumor-bearing mice, but improved the survival of cachectic mice. Mice receiving erythropoietin had increased erythrocyte and platelet counts, but significantly decreased white blood cell count. In addition, erythropoietin administration significantly decreased interleukin-6 levels, not only in serum but also in the inoculated tumor. These results indicate that the positive therapeutic effects of erythropoietin on cancer cachexia are due, not only to improving metabolic and exercise capacity via an increased erythrocyte count, but also to attenuation of cachectic manifestations by decreased production of the cachexia-inducing cytokine, interleukin-6.