The aim of this study was to determine: (1) whether the Short Chain Fatty Acids (SCFA) Acetate, Propionate, and Butyrate enhance the synthesis and secretion of intestinal apolipoprotein A‐IV‐containing lipoproteins and (2) if so, whether these particles are able to promote cholesterol efflux in vitro. For this purpose Caco‐2 cells were used for their functional properties of differentiated enterocytes. They were incubated with the three SCFA (2, 4, and 8 mM) for 48 h. Only butyrate stimulated apoA‐IV gene expression and this was associated with an increase in apoA‐IV secretion. A nondenaturing 2D‐PAGE (agarose gel was followed by PAGE) was used to identify apoA‐IV‐containing lipoproteins in various media, and showed that butyrate stimulated the secretion of two small HDL sized particles. The influence of these secreted particles on cholesterol efflux was investigated using incubation of media with ³H‐cholesterol‐labeled Fu5AH cells. The data indicate that conditioned media from Caco‐2 cells treated with butyrate resulted in an increase of 20–30% in cholesterol efflux. We conclude that butyrate may regulate apoA‐IV secretion and, therefore, modulate reverse cholesterol transport. J. Cell. Biochem. 83: 230–238, 2001. © 2001 Wiley‐Liss, Inc.