Abstract: The sub chronic esculetin (6,7-dihydroxy-coumarin)-induced response on malondialdehyde concentration and some haematological and lipid metabolism parameters was studied in normal male Wistar rats to further understand the underlying esculetin metabolism and effects. Five groups (n = 6) of rats, A-E were respectively exposed to 6.0, 12.0 and 24.0 mg kg–1 b.wt. of esculetin, 0.2 mL of the vehicle control (10% dimethylsulfoxide (DMSO)) and 0.2 mL of the normal control (Distilled Water (DW)) per orally and daily for 28 days. Compared with the controls, the haematological parameters change in the esculetin-exposed rats was not significant (p>0.05) but decreased numerically with increasing dose viz: hemoglobin (99.83±5.04 g L–1-91±7.04 g L–1), packed cell volume (30±1.41%-27.33±2.16%), white blood cell count (9.63±0.91×109 L–1-7.95±0.58×109 L–1), neutrophil (1.93±0.51×109 L–1-1.72±0.34×109 L–1) and lymphocyte count (7.64±1.04×109 L–1-6.18±0.63×109 L–1). The reduction in the serum cholesterol (3.39±0.23 mmol L–1-3.01±0.78 mmol L–1) and triacylglyceride (0.49±0.45 mmol L–1-0.15±0.05 mmol L–1) concentrations in the esculetin-dosed rats was significant (p<0.05) and followed the numerical decreasing trend. The serum MDA concentration (1.90±0.53 mmol L–1-2.82±1.50 mmol L–1) decreased (p<0.05) but increased numerically with increasing dose. Thus, the sub-chronic esculetin-induced alteration was inversely related to esculetin dose and may not have resulted to significant pathologies or dysfunctional states in the rats.