Zapoteca portoricensis (Jacq) HM. Hernández popularly called “Elugelu” belongs to the Fabaceae family. It is reportedly used in traditional medicine as anti-diarrhoea, anticonvulsant, antispasmodic and in management of autoimmune disorders. The immunomodulatory activity of methanol root extract and fractions of Zapoteca portoricensis was evaluated using three experimental models: neutrophil adhesion, haemagglutination antibody (HA) titre and delayed hypersensitivity (DTH) of an immune response in mice. Five (5) groups of mice (n=5) were used; group I was the normal control; group II was the standard control (levamisole, 2.5 mg/kg) while groups IIIA–C, IVA–C and VA–C received graded doses (25, 50, 100 mg/kg) of methanol extract (ME), ethyl acetate fraction (EF) and methanol fraction (MF), respectively. Sheep red blood cells (SRBCs; 0.1 ml) were injected subcutaneously to sensitize the animals. The study results showed that the methanol fraction (MF) exhibited the highest percentage (46.12%) in neutrophil adhesion followed by the ethyl acetate fraction (EF) (37.06%) at 100 mg/kg dose, respectively, compared with the normal control. The highest percentage increase in both primary and secondary antibody titre was found to be ME (85.19%, 43.20%), EF (91.53%, 102.67%) and MF (128.31%, 111.89%) at 50 mg/kg dose, respectively compared to the normal control. The EF at the doses of 25 and 50 mg/kg produced the highest percentage inhibition (56.57%, 58.33%) in DTH response, respectively, followed by MF (42.46%) at a dose of 25 mg/kg. Oral administration of Z. portoricensis exhibited immunomodulatory effects on specific components of the immune system in mice.