BackgroundPropionic acid is a three-carbon short chain fatty acid (SCFA) that has various effects on colonic functions. Although several studies have shown the effects of propionic acid on intestinal mucosal barrier function, studies of the promotion effect during pre-weaning are rare in the literature as far as we know.MethodsPre-weaning male Sprague-Dawley rats 7 days after birth were given an oral 0.2 mL/10 g of 200 mM propionic acid solution in the propionic acid group or normal saline solution in the control group by gavage twice a day for ten days. The proximal colonic contents were used for extraction and determination of propionic acid by gas chromatographic analysis; the transepithelial electrical resistance (TER) of colonic tissue was detected by an Ussing chamber; the alterations of ZO-1, Claudin-1, Claudin-8 and Occludin proteins were analyzed by Western blot and immunohistochemistry; and The activity of ERK and p38 MAPK was determined by the phosphorylation status of ERK1/2 and p38 with Western blot.ResultsOur results suggested a higher concentration (23.5 ± 1.9 mmol/kg) of propionic acid compared to the physiological concentration (18.1 ± 0.9 mmol/kg) in colonic contents after oral administration increased the value of TER and the expression of ZO-1, Claudin-1, Claudin-8 and Occludin compared to the control group. Furthermore, the expression levels of phosphorylated ERK1/2 and p38 MAPK were increased in propionic acid group.ConclusionsWe concluded that continuous oral administration of propionic acid during lactation may increase its concentration in the proximal colon and promote epithelial barrier function of proximal colon by enhancing the expression of ZO-1, Claudin-8, Claudin-1 and Occludin via increases in the expression of ERK1/2 and p38 MAPK.