The present study aims to access the effects of sophora alkaloids on the production of pro-inflammatory cytokines and evaluate their therapeutic efficiency on cachexia. The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-α and IL-6 production in both RAW264.7 cells and murine primary macrophages, and sophocarpine showed the most potent inhibitory effect among them. Quantification of TNF-α and IL-6 mRNA in RAW264.7 cells by real-time RT-PCR revealed that both sophocarpine and matrine suppressed TNF-α and IL-6 expression and sophocarpine has stronger suppressing potency than matrine. Inoculation (s.c.) of colon26 adenocarcinoma cells into BALB/c mice induced cachexia, as evidenced by progressive weight loss, reduction in food intake, wasting of gastrocnemius muscle and epididymal fat, and increase in serum levels of TNF-α and IL-6. Administration of 50 mg/kg/d sophocarpine or matrine for 5 days from the onset of cachexia did not inhibit the tumor growth but resulted in attenuation of cachexia symptoms. Furthermore, sophocarpine and matrine decreased the serum levels of TNF-α and IL-6, and sophocarpine showed a better therapeutic effect than matrine. These results suggest that sophocarpine and matrine exert anti-cachectic effects probably through inhibition of TNF-α and IL-6.