This research article published by International Journal of Biosciences, Vol. 16, No. 1, 2020Organophosphates (OPs) pesticides are reported to cause acute poisoning because of their ability to inhibit acetyl cholinesterase enzyme (AChE). Available antidotes drugs are atropine sulfur, Pralidoxime (2-pyridine aldoxime methyl chloride) and diazepam, which act to recover OP-AChE inhibition. These are controlled drugs not easily accessed and very expensive. In this present study Acacia nilotica was assessed for its antioxidant activity, and in vivo AChE depression and recovery from OP-AChE inhibition. The mice were exposed in three different OPs including chlorpyrifos 480g/l (CPF), Fenitrothion 10g/l (FNT) and Profenophos 720g/l (PFP). The methanolic bark extract of A. nilotica had a substantial increase of absorbance readings from 2.895±0.0032 to 3.716±0.0259 compared to standard (ascorbic acid) from 0.108±0.0033 to 1.468±0.0297 at P<0.05. AChE depression and recovery were assessed by using the AChE test mate kit to analyze blood collected from the mice’s tail. Recovery effect under crude methanolic extract from A. nilotica, ascorbic acid and normal feeding were compared with the untreated group. Results have shown that there is a significant decrease of AChE level from Day zero to 14th day in all treated groups of CPF, PFP and FNT which indicate poisoning. Significance of AChE recovery observed only in male mice in all treatment groups. This is a first study to assess and report the antioxidant activity of stem bark methanolic extracts of A. nilotica in controlling organophosphate pesticide toxicity in mice, hence further studies on isolation of active compounds are recommended.