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Various studies have suggested a link between vitamin A (VA), all-<i>trans</i>-retinol, and type 2 diabetes (T2D). However, the functional role/expression of vitamin A receptors (<i>Rarα</i>, <i>β,</i> and <i>γ</i>) in pancreatic β-cells is not clear yet. Accordingly, we performed a series of bioinformatics, molecular and functional experiments in human islet and INS-1 cells to evaluate the role of <i>Rarβ</i> on insulin secretion and pancreatic β-cell function. Microarray and RNA-sequencing (RAN-seq) expression analysis showed that <i>RARα</i>, <i>β,</i> and <i>γ</i> are expressed in human pancreatic islets. RNA-seq expression of <i>RARβ</i> in diabetic/hyperglycemic human islets (HbA1c ≥ 6.3%) revealed a significant reduction (<i>p</i> = 0.004) compared to nondiabetic/normoglycemic cells (HbA1c < 6%). The expression of <i>RARβ</i> with <i>INS</i> and <i>PDX1</i> showed inverse association, while positive correlations were observed with <i>INSR</i> and HbA1c levels. Exploration of the T2D knowledge portal (T2DKP) revealed that several genetic variants in RARβ are associated with BMI. The most associated variant is rs6804842 (<i>p</i> = 1.2 × 10⁻²⁵). Silencing of <i>Rarβ</i> in INS-1 cells impaired insulin secretion without affecting cell viability or apoptosis. Interestingly, reactive oxygen species (ROS) production levels were elevated and glucose uptake was reduced in <i>Rarβ</i>-silenced cells. mRNA expression of <i>Ins1</i>, <i>Pdx1</i>, <i>NeuroD1</i>, <i>Mafa</i>, <i>Snap25</i>, <i>Vamp2</i>, and <i>Gck</i> were significantly (<i>p</i> < 0.05) downregulated in <i>Rarβ</i>-silenced cells. For protein levels, Pro/Insulin, PDX1, GLUT2, GCK, pAKT/AKT, and INSR expression were downregulated considerably (<i>p</i> < 0.05). The expression of NEUROD and VAMP2 were not affected. In conclusion, our results indicate that <i>Rarβ</i> is an important molecule for β-cell function. Hence, our data further support the potential role of VA receptors in the development of T2D.