Abstract The immunomodulatory effect of the ethanolic leaf extract of Phyllantus amarus on wistar rats was investigated. Twenty eight (28) male animals were used for the study. The animals were divided into four (4) groups of seven (7) animals each. Group 1 was the normal control and received distilled water, animals in group 2 were given low dose (7.1 mg/kgBW) of the extract, group 3 were given medial dose (14.1mg/kgBW) and group 4 were given high dose (28.3 mg/kgBW) of the extract. The treatment was administered twice daily for twenty eight (28) days after which the animals were sacrificed and blood samples used for analysis where obtained via cardiac puncture. The phytochemical screening of the plant was carried out and results shows that the plant contains flavonoids, saponins, alkaloids, terpenes, phenols, steroids, glycosides and tannin. Results reveal that the group treated with low (102.41±7.41), medial (101.84±11.72) and high dose (100.94±30.47) recorded an elevated WBC value when compared with the control (83.20±11.30) at p<0.05 significant level. Similar trend was observed for lymphocytes. The extract recorded no effect on monocytes and eosinophils counts. More so, the plants extract lowers the CD4, T-cells and B-cells count at p<0.05 significant level compared with the control, suggesting that the extracts have anti-microbial properties to lower infections and hence the decreased values observed. Owing to this phytochemical constituents, it also suggests that the extract have the ability to suppress inflammatory diseases and auto-immune diseases occasioned by CD4. Conclusively, ethanolic Phyllantus amarus leaf extract is a good immunomodulatory agent at recommended dose range of 7.1 to 28.3mg/kg.