In the present study, we evaluated and tested the antibacterial activity both aqueous and ethanolic extracts of Melia azedarcha (stem and leaves), against pathogenic E coli in vitro and in vivo. One hundred Guinea pigs of 1-2 month old were divided into 5 equal groups each (20). Control (Gp.1) did receive neither viable bacteria nor treatment. Each animal from the other groups (Gp2-5) was challenged with (1-2×108 ) viable E coli in 200 µL normal saline (0.9%) through IP route. GP-2 infected group treated with 200-µL saline IP and kept as positive control group. (Gp.3-4) are infected treated with Melia azedarcha (aqueous leave extract) with a dose 65 and 130 mg/400gm BW respectively.Gp-5 infected treated group with cephoperazone antibiotic at dose 60 mg/400gm BW. The treatment by drug or the extracted medicinal plant was started 72h post- infection for 7 successive days. Serum and whole blood sample were collected from all groups 7 th and 14th days post treatment to evaluate some hematological and biochemical changes as well as immunomodulatory cytokines TNF-α . Oral treatment of the plant extract caused significant benefit results in infected guinea pig appeared in the correction of some hematological and biochemical parameters also try to suppressed inflammatory cytokine response represent in TNF-α. From the present work, it could be concluded that Melia azedarach extract differ in efficacy according to the used dose, as appeared, the low dose used not completely effective also Cefoperazone drug is effective antibacterial drug, which cause some transient hematological and biochemical changes..