Aging is epitomized by a progressive increase in neuroinflammation which is associated with altered brain states, neuronal death and eventually neurodegeneration disease. Microglia are the resident macrophagic cells of the brain that play a crucial role in maintaining homeostasis and immune response especially during neuroinflammation. The endocannabinoid system (ECS) is a negative feedback signalling system that helps to maintain homeostasis. The ECS is able to modulate microglia activation states and functions through the endocannabinoid receptors CB1 and CB2. Although, the role of ECS and microglia in neuroinflammation have been studied independently, their relation is far less explored especially during aging. This study establishes a connection between ECS and microglia functionality during neuroinflammation by using CB1 receptor agonist (ACEA) and antagonist (ribonabant) as well CB2 receptor agonist (JWH133) and antagonist (AM630) on primary aged mouse microglia treated with LPS. After which, microglia activation and functionality experiments were performed for phagocytosis and oxidative stress (ROS) and related gene expressions. We demonstrated that in the presence of an CB1 agonist (ACEA) phagocytosis increases with increasing concentration of agonist and subsequently ROS decreases with increasing concentrations. However, opposite effect for both phagocytosis and ROS production was observed in the presence of CB1 antagonist (ribonabant). In the presence of an CB2 agonist (JWH133) phagocytosis and ROS decreased with increasing concentrations where CB2 antagonist (AM630) had the opposite effect for both phagocytosis and ROS which increased with increasing concentrations of antagonist. To conclude, the modulation of the ECS could reduce neuroinflammation in aged microglia.