In this study mice were percutaneously exposed to 50 S. mansoni cercariae. Seven weeks post infection (pi), infected mice were either injected i.p. a single dose of alloxan (200 mg kg-1 ) or treated with a single dose of alloxan followed, three days later, with daily i.p. treatment of ethanolic extract of Cleome droserifolia (0.31 g kg-1 ) for 18 days. Diabetes mellitus (DM) affected characteristics of Schistosoma infection as shown in alteration of oogram pattern, impairing of egg maturation and lowering of faecal egg output. However, extract treatment (EXT) affected the previously mentioned aspects in addition to its remarkable effect on worm load, diminishing of hepatic granulomas and suppressing the formation of involutional granulomas. Results indicated that DM increased the complications of schistosomiasis that was manifested by the augmented increase of serum glucose level, the severe decrease of serum thyroid hormones (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), insulin levels, liver glycogen content and hepatic DNA. In addition, a decrease in hepatic GSH that was accompanied by an increase in serum uric acid were observed in infected-DM mice. Serum total proteins concentrations were obviously decreased and some of protein fractions were also decreased or absent in both infected and infected-DM mice except for gamma globulin that was increased in both groups. EXT succeeded efficiently to alleviate these alterations in infecteddiabetic mice, to various extents. The beneficial effects of EXT on thyroid and pancreatic hormones status seem to be contradictory to its beneficial anti-schistosomiasis effects. This contradiction may suggest that EXT exerts its beneficial effects through its direct effects on the parasite, not secondary to its effect on the host. The current results showing differential effects of both diabetes and extract on schistosomiasis, though both are beneficial, serve to corroborate this hypothesis.