Medicinal plants are rich in phytochemicals compounds that can be beneficial for livestock production and for treatment of human diseases. This study was designed to compare biochemical, haematological and histopathological changes in rats treated with different fractions and doses of Citrullus lanatus rind (CLR). The powdered CLR was extracted with ethanol, later fractionated with different solvents (n-hexane, chloroform, ethanol) and crude ethanol extract subsequently labelled as CLRH, CLRC, CLREF and CLRCE respectively. This study was done with forty male Wistar rats randomly assigned to thirteen groups. Group A received 10ml/kg distilled water; groups B1, B2 and B3 received 100,800 and 160mg/kg CLRH respectively; groups C1, C2 and C3 received CLRC; groups D1, D2 and D3 received CLREF; groups E1, E2 and E3 received CLRCE dosages were administered similar to group B, these were done daily for 14 days. Blood and liver samples were subjected to haematological, serum biochemistry and histopathological analysis. Data were evaluated with differences between groups by analysis of variance, P<0.05 considered significant using Graphpad prism. The PCV (50.00±1.16% versus 48.50±0.65%) and leucocytes (9.37±0.71x103cell/µl versus 9.11±0.02 x103cell/µl) of rats treated with 1600mg/kg CLRCE were significantly high, while AST (18.00±1.16iu/Lversus 13.50±0.65iu/L) of rats treated with 1600mg/kg CLRH were significantly high when compared with rats treated with distilled water. Meanwhile there were congested central vein, hepatic atrophy and sinusoidal dilatations in liver of rats treated with 1600mg/kg of CLRC. It was concluded that CLR in ethanol is safe and improves haematological and biochemical parameters.