Medicinal plants and herbal drugs have widely been used in several diseases which contain highly active pharmacological agents. Several previous studies have mounted about the hepatotoxicity of these remedies which ranges from mild enzyme alterations to liver failure in humans and animals. This study aimed to evaluate the toxicity profile of the crude methanolic seed extract of Calliandra surinamensis on rat liver functions. An acute toxicity study was carried out using modified Lorke’s method and sub-chronic toxicity was done following the Organisation for Economic Cooperative and Development guidelines with testing chemicals 423 and 407 to assess the effect of the seed extract on liver function alongside histopathology assessment of the liver. The haematological indices revealed no significant change in red blood cells and other haematological parameters. The average organ weight of the tested rats showed no significant differences. The histopathological examinations of the rat liver revealed no observable toxic injury to the tissue after treatment with the seed extract across all concentrations. There were desirable morphological vasoactive changes of dilatation and active congestion in the organ across all the concentrations which were dose-dependent. There was induced activation of the sinusoidal kupffer cells, which signified a boost to the local immune system of the liver. The nucleoli in the hepatocyte nuclei were remarkably conspicuous which implied an increase in the production of ribonucleic acid that is deployed in protein synthesis.