Paraquat is one of the most common and acutely toxic herbicides used in developing nations, with epidemiological studies linking chronic paraquat exposure to Parkinson’s disease. Numerous studies in mice have demonstrated a chronic paraquat-mediated reduction in dopaminergic neural markers in the midbrain. However, given the scarcity of research surrounding the effect of chronic paraquat on striatal neurotoxicity, there is a need for further investigation into the effect of paraquat on the induction of endoplasmic reticulum stress and inflammation in mouse striatum. This study attempts to observe changes in both inflammatory and endoplasmic reticulum stress markers in mouse striatum following chronic paraquat administration. Furthermore, previous studies have shown that inhibition of soluble epoxide hydrolase mitigates MPTP-mediated loss of dopaminergic neurons and endoplasmic reticulum stress in mouse striatum. Thus, this study seeks to determine if inhibition of soluble epoxide hydrolase mitigates paraquat-induced neurotoxicity, as well as whether epoxyeicosatrienoic acids, endogenous substrates of the soluble epoxide hydrolase, reduce TLR4-mediated inflammation in primary astrocytes and microglia. Our results show that while the pro-inflammatory effect of chronic paraquat injection on mouse striata is relatively small, there are significant inductions of inflammatory and cellular stress markers such as COX2 and CHOP in vivo and inflammatory markers in vitro that can be mitigated through a prophylactic administration of a soluble epoxide hydrolase inhibitor.