Background: Major Depressive Disorder (MDD) is a prevalent and debilitating psychiatric condition with multifaceted etiology. Emerging indication recommends that neuroinflammation plays a pivotal part in pathophysiology of MDD, offering new avenues for therapeutic interventions. Our current research seeks to discover the intricate association among neuroinflammation and MDD, shedding light on potential targets for innovative psychiatric treatments. Aim: The primary goal of our current research is to expansively investigate part of neuroinflammation in Major Depressive Disorder and discern its implications for development of novel psychiatric therapeutics. By elucidating the molecular and cellular mechanisms involved in neuroinflammation, we aim to identify potential therapeutic targets to enhance treatment strategies for individuals with MDD. Methods: This study employs a multi-faceted approach, combining clinical observations, neuroimaging techniques, and molecular analyses. A cohort of individuals diagnosed with Major Depressive Disorder will undergo comprehensive assessments, including neuropsychological evaluations and neuroinflammatory biomarker measurements. Advanced imaging technologies, such as fMRI and PET scans, will be utilized to visualize and quantify neuroinflammatory processes. Additionally, preclinical models will be employed to elucidate causal relationships and explore the impact of neuroinflammation on depressive-like behaviors. Results: Preliminary findings reveal a significant correlation between elevated neuroinflammatory markers and the severity of depressive signs in individuals through Major Depressive Disorder. Neuroimaging data demonstrate alterations in key brain regions associated with neuroinflammation, providing insights into the neurobiological underpinnings of MDD. Furthermore, preclinical models highlight potential therapeutic targets within the neuroinflammatory cascade. Conclusion: This study underscores the critical role of neuroinflammation in Major Depressive Disorder, emphasizing its potential as a target for novel psychiatric therapeutics. The integration of clinical and preclinical data contributes to the more complete understanding of intricate interplay between neuroinflammation and MDD. The identification of specific molecular targets opens avenues for the development of targeted interventions that may revolutionize the treatment landscape for individuals affected by MDD.