Introduction: Annona muricata is a lowland tropical fruit bearing tree of the Annonaceae family which can be found in the rainforest of Africa, South America, and Southeast Asia. It is commonly known as soursop, graviola, guanabana, or brazillian pawpaw. It has a large, glossy, dark green leaves with edible, green heart-shaped fruit. The leathery skin of the fruit is covered with soft, curved spines each of which may contain 55-170 black seeds distributed in a creamy white flesh with a characteristic aroma and flavour. Objectives: The study aims to investigate the effect of ethanol extract of Annona muricata on Lipopolysaccharide induced Neuroinflammation in Wistar rats. Method: Prostagladin E1 & E2 markers were used for biochemical assays. The Neurobehavioral assessment of memory and locomotion coordination was assessed using the Y maze and Open field and the data was presented as Mean ± Standard Error of Mean (SEM). Statistical analysis was performed by one-way analysis of variance (ANOVA) followed by a post hoc Newman-Keuls multiple comparison test. All statistical analysis were done by using Prism software, version 5 (GraphPad software Inc., San Diego, CA, USA). Results: The effects of ethanol extract of Annona muricata (AME) on PGE1 on lipopolysaccharide induced neuroinflammation in wistar rats shows the control, LPS, AME + LPS and Donepezil + LPS. From the result, LPS + Extract (AME) showed significant effects when compared to LPS which showed no significant effect when compared to control. The effects of ethanol extract of Annona muricata (AME) on % Alternation on lipopolysaccharide induced Neuroinflammation in wistar rats shows the control, LPS, AME + LPS and Donepezil + LPS. From the result LPS + Extract (AME) showed significant effects when compared to LPS. LPS showed no significant effect when compared to control. The effects of ethanol extract of Annona muricata (AME) on No of entry on lipopolysaccharide induced neuroinflammation in wistar rats shows the control, LPS, AME + LPS and Donepezil + LPS. From the result LPS + Extract (AME) showed no significant effects when compared to LPS which showed significant effect when compared to control. Conculsions: This study concludes that Annona muricata, at 200mg/kg possess excellent antiinflammatory qualities and it could be further explored as a potential choice for the treatment of neurodegenerative diseases.