Abstract: Background: The folkloric claim that Cnidoscolus aconitifolius (Chaya) could ameliorate anaemia requires scientific revalidation in anaemic models. Objective: The aim of this study is to investigate the anti-anaemic effect of Cnidoscolus aconitifolius on cyclophosphamide-induced anaemia in rats. Methods: The leaves of Cnidoscolus aconitifolius were collected, dried and extracted with ethanol. Twenty five Wistar Albino rats weighing 120–180 kg were used. Anaemia was induced in groups 2, 3, 4 and 5 with a single injection of cyclophosphamide, while group 1 served as a negative control without anemia and was treated with 0.5 mL of normal saline, Group 2 rats were treated with 100 mg/kg body weight of Cnidoscolus aconitifolius. Group 3 rats were treated with 500 mg/kg body weight of Cnidoscolus aconitifolius. Group 4 served as the positive control rats and was treated with 0.5 mL of normal saline. Group 5 which served as the standard control rats and were treated with 5 mg/kg body weight of standard drug Chemiron. The treated lasted for two weeks during which blood samples were collected from each rat for haematological analysis. Results: The result shows that hematological parameters were elevated in groups 2, 3 and 5 rats treated with 100 mg/kg and 500 mg/kg body weight of ethanol extract of Cnidoscolus aconitifolius and chemiron respectively. Conclusions: Ethanol leaf extract of Cnidoscolus aconitifolius at a graded dose of 500 mg/kg body weight had higher ameliorative effect on the haematological parameters of cyclophosphamide-induced anemia in rats.