As a central immune organ unique to birds, the bursa of Fabricius (BF) provides a proper microenvironment for B-cell development. The bursal B-cells undergo rapid proliferation and differentiation at the embryonic stages, but 95% of them undergo apoptosis after hatching. Few studies have focused on the cause of bursal B-cells apoptosis at the embryonic stages in birds. To explore the cause, we compared the transcriptional profiles of three characteristic embryonic stages in duck, including embryonic day 14 (ED14), 22 (ED22) and 1 day after hatching (D1). Our results showed that the apoptotic B-cells were first observed at ED22 while there were no apoptotic B-cells at ED14. By performing enrichment analysis for DEGs and qRT-PCR, our results demonstrated that both mitochondrial and Fas signaling pathways mediated bursal B-cell apoptosis during the duck embryonic development. Further, protein-protein interactions (PPIs) and KEGG enrichment analysis together showed that BMP4, FoxO1 and IGF-1 may regulate bursal B-cells apoptosis. In addition, the DEGs showed two stage-specific expression patterns. By analyzing the genes of two expression patterns, the results indicated that B-cell false differentiation may be one of the reasons of apoptosis in the duck embryonic BF. Overall, these data demonstrated that from ED14-ED22, apoptosis of bursal B-cells was mediated by mitochondrial and Fas signaling pathways and could be regulated by BMP4, FoxO1 and IGF-1 in duck. One of the primary causes of bursal B-cell apoptosis may be false differentiation in B-cells.