We have examined the effects of differentiation on responsiveness of human LS174T and HT‐29Cl.16E goblet cells (GC) to the inflammatory mediator IL‐13. Expression of the GC genes mucin 2 (MUC2), resistin‐like molecule beta (RETNLB), and trefoil factor 3 (TFF3) and the sulfotransferase (ST) genes carbohydrate (N‐acetylglucosamine 6‐O) sulfotransferase 5 (CHST5) and beta‐galactose‐3‐O‐sulfotransferase 2 (GAL3ST2) was measured at different stages of confluence and after stimulation with IL‐13 using RT‐qPCR. Sialo‐ and sulfomucin chemotypes were assessed by high iron diamine and alcian blue (HID/AB) staining. Expression of MUC2, TFF3, and RETNLB increased in HT‐29Cl.16E cells with days post‐confluence, consistent with GC differentiation, and with addition of IL‐13 to pre‐confluent cells. However, MUC2 and RETNLB expression decreased while TFF3 expression was unaltered in the more differentiated, post‐confluent HT‐29Cl.16E cells treated with IL‐13. CHST5 expression increased 20‐fold in pre‐confluent cells, but only 10‐fold in post‐confluent cells treated with IL‐13. Expression of CHST5 also increased in LS174T cells in response to IL‐13. HID/AB analysis corroborated an increase in sulfomucin production in response to IL‐13. Together the data demonstrate that IL‐13 modulation of GCs is dependent on state of differentiation and may stimulate mucin sulfation via effects on the CHST5 gene.