One hundred and ninety-three Sprague-Dawley (SD) rats (average body weight 100-120g) were randomly divided into five groups (I-V). Groups I and II rats served as the negative and positive controls respectively and both received 0.1mg/kg Se from sodium selenite supplemented diets for the 18-week experimental period. Groups III-V rats were fed Se from SEM supplemented diets (0.3, 1 and 3mg/kg respectively). To induce hepatocarcinoma, groups II-V rats received diethylnitrosamine solution (100mg/L) at the dosage of 10mg/kg body weight in drinking water daily for 16 weeks, followed by sterilized water for a further 2 weeks. Group I rats received sterilized water throughout. At weeks 4, 8, 12 and 16 five rats in each group were sacrificed by cervical decapitation. At the termination of the study, at week 18, the surplus rats were sacrificed by cervical decapitation. Feed was withheld from the rats for 12 h before sampling. The following items including TNF-alpha, IGF-II, NO and T-NOS levels in plasma were tested using kit techniques. At the same time the expression of vascular endothelial growth factor (VEGF) in tumor tissue was analyzed by immunohistochemistry using the envision two-step methods with a kit. The results indicated that SEM could increase the levels of TNF-alpha in the early stages of hepatocarcinoma formation, however there was a decrease in the later stage of hepatocarcinogenesis. SEM could also significantly decrease the levels of IGF-II and NO, and inhibit the expression of VEGF in tumor tissue. SEM delayed the development of hepatocarcinoma in rats and that could be partially attributed to inhibition of angiogenesis.