<p>Type 2 Diabetes Mellitus (T2DM) is a multifaceted disorder with increasing global prevalence, characterized by chronic hyperglycemia, insulin resistance, and associated complications. Recent research has revealed micro-RNAs (mi-RNAs) as key post-transcriptional regulators participating in metabolic and inflammatory pathways relevant to T2DM pathogenesis. Among these, miR-21-5p has gained attention for its potential role in modulating gene expression linked to disease progression. The present study elucidated the expression profile of miR-21-5p in peripheral blood mononuclear cells (PBMCs) of T2DM patients from the Himalayan Kashmir region and evaluated its association with clinical and biochemical parameters. A total of 100 T2DM patients as cases and 40 healthy subjects as controls were enrolled. PBMCs were isolated from whole blood, and total RNA was isolated via TRIzol reagent protocol. The expression of miR‑21-5p was quantified using SYBR Green-based real‑time quantitative PCR, with U6 RNA as the endogenous control. The analysis revealed a statistically significant upregulation of miR-21-5p in T2DM patients as compared to healthy subjects (p &lt; 0.05). Nevertheless, no statistically significant association was observed between miR-21-5p expression and clinical variables such as HbA1c, blood pressure, body mass index (BMI), serum urea, or creatinine levels. A non-significant trend toward increased expression in male patients was noted. These findings suggest that miR-21-5p may serve as potential biomarker for T2DM, independent of traditional clinical parameters. Moreover large-scale, multi-ethnic studies are required to validate its diagnostic and prognostic significance and to gain deeper insights into its function in the molecular landscape of T2DM.</p> Graphical abstract <p></p>