Catch-up growth is always companied with later development of obesity and osteoporosis that are two interrelated clinical entities. However, the potential mechanism of the link between them during catch-up growth is unknown. Rats were divided into two groups. Rats of the normal control (NC) group were offered ad libitum access to food, while rats of CUGFR group were food restricted for 4 weeks, and then were allowed full access to food for 0, 2, 4 weeks, respectively. The fat percentage and distribution, bone mineral density, biochemical and histological indexes of bone were detected. Moreover, the expression of adipogenic or osteoblastic differentiation-related genes of mesenchymal stem cells (MSCs) was also determined. Catch-up growth led to a rapid visceral fat accumulation. Although there was no difference in the histological indexes of bone between NC group and CUGFR group, the bone turnover marker, serum Bone Gla-protein (s-BGP), decreased in CUGFR group. The adipogenic differentiation-related gene of MSCs, PPAR-gamma, was significantly higher than that of NC group especially when catch-up growth for 4 weeks. Nevertheless, the osteoblastic differentiation-related gene of MSCs, Runx2, was increased but failed to reach the levels of the controls eventually. Both protein and mRNA of TAZ, a main transcriptional modulator of MSCs differentiation, failed to catch up even after being allowed full access to food for 4 weeks. CUGFR induces the differential differentiation of MSCs, potentially suppressing bone formation and favoring catch-up fat, which might be responsible for the increased risk of osteoporosis and obesity during CUGFR.