Long non-coding RNAs (lncRNAs) are transcripts with a length of more than 200 nucleotides that lack protein-coding capacity. LncRNAs play important roles in the regulation of genes during many biological processes, development and disease progression, such as obesity. Obesity is an increasing health concern around the world. Although multiple studies linking lncRNAs and fully differentiated adipocytes have been published, the systematic analysis of those lncRNAs involved in early preadipocyte differentiation, when fate determination decisions are made, has not been reported. In order to fill this gap, we conducted strandspecific RNA-Seq on mouse 3T3-L1 preadipocyte cells and compared the expression profiles before and after early differentiation for 2 days. We identified 82 lncRNAs that significantly changed their expression after early differentiation, 98% of which were newly discovered in association with early adipogenesis. The most remarkable lncRNAs were U90926, Wincr1, Kcnq1ot1, Malat1 and Hotairm1. Expression patterns for these identified genes were also highly correlated with markers of adipogenesis, including PPAR, CEBP, FABP4 and FASN. Further analysis implies that many of those altered lncRNAs might coordinately inhibit Wnt/-catenin signaling pathway to promote preadipocyte differentiation. This work strongly suggests that lncRNAs are critical in the proliferation and differentiation of adipose tissue.