It is generally accepted that Propionibacterium acnes (P. Acne) is involved in the development of acne, while the mechanisms of sebaceous lipogenesis and its control is unclear. Enterococcus faecalis FK-23 had shown to promote an anti-inflammatory action in several animal models. In the current study, we examined whether FK-23 modulate lipogenesis in sebocytes. FK-23 stimulated lipogenesis, while inhibited them in the presence of P. Acne. FK-23 acutely inhibited acetyl-CoA carboxylase (ACC) phosphorylation levels, while stimulated them with P. Acne. FK-23 stimulated PPARγ expression and activity, while inhibited them with P. Acne as pioglitazone did. These combined evidences demonstrated that the dual action by FK-23 on lipogenesis should reflect differentiation machinery prior to PPARγ, leading to producing adequate levels of sebum.