Abstract This study investigated the effect of Dendrobium officinale polysaccharide (DOP) on the adipogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). DOP was extracted fresh Dendrobium officinale. Rat BMSCs were prepared, and then were treated with 0 (control), 50, 100, 200, 400, 800 μg/mL DOP, respectively. The cell viability was determined by MTT assay. The adipogenic differentiation was quantitatively analyzed by oil red O staining assay. The mRNA expressions of adipogenic differentiation related gene peroxisome proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4) were detected by RT-PCR. Results showed that, DOP with 0-800 μg/mL concentration had no significant toxicity to BMSCs. 200-800 μg/mL DOP could obviously inhibit the adipogenic differentiation of BMSCs. Compared with control group, the expression levels of PPARG, LPL and FABP4 mRNA 200, 400 and 800 μg/mL DOP groups were significantly decreased (P < 0.05 or P < 0.01). DOP can inhibit the adipogenic differentiation of BMSCs, which may be related with its down-regulation of PPARG, LPL and FABP4 expressions in BMSCs.