The oral toxicity of both insecticides: the neonicotinoid Thiamethoxam (TMX) and the avermectin Emamectin Benzoate (EB) was conducted daily in female rats with doses of 25, 50, 100 mg/kg/body weight (bw) for TMX and 1.25, 2.5, 5 mg/kg bw for EB for 90 successive days. Significant decrease in the body weight gain and food consumption was observed at highest dose (100 mg/kg bw) of TMX and (5 mg/kg/ bw) of EB and at necropsy the relative body weights of liver and kidney was also significantly increased at this dose level. There were no significant changes in hematological parameters for TMX, while the high dose of EB significantly decreased in all the investigated hematological parameters. In clinical chemistry parameters a significant increase (p < 0.05) was noted in serum AST, ALT, ALP and BUN in animals exposed to 100 mg/kg bw dose of TMX and 5 mg/kg bw of EB. On the other hand, at the same levels there was a dose-depended significant decrease in serum total protein and albumin. Oral administration of TMX and EB to female rats for 90 days resulted in 16–30% and 15–26% inhibition of serum cholinesterase (ChE) activity, respectively. Liver and kidney of rats exposed with high dose of TMX and EB had showed mild pathological changes. Based on the hematological, biochemical and histpathological studies it is evident that TMX and EB has not produced any significant effects at 20 and 1.25 mg/kg bw doses respectively but induced toxicological effects at 100 mg/kg bw for TMX and 5 mg/kg bw for EB to female rats. Hence, 25 mg/kg bw/day for TMX and 1.25 mg/kg bw/day for EB dose may be considered as No Observed Effect Level (NOEL) for female rats for both insecticides respectively.