Abstract: A new type of insulin delivery system capable of better self-regulating the release of insulin was reported in this study. This insulin delivery system was made of a low crosslinked insulin-imprinted hydrogel that exhibited pH-dependent interpolymer interactions between poly(methacrylic acid) (PMAA) and poly(ethylene glycol) (PEG). At acidic conditions (such as pH 3.5), this delivery system resembled a highly crosslinked imprinted hydrogel and demonstrated a relatively slow release due to the formation of the PMAA-PEG complexes, which significantly increased physical crosslinking within the hydrogel interior and largely fixed the imprinted networks. On the contrary, at neutral or basic conditions (such as pH 7.4), this delivery system was comparable to a non-imprinted hydrogel and caused a rapid release resulting from the dissociation of the PMAA-PEG complexes. Unlike previously reported non-imprinted hydrogels and highly crosslinked imprinted polymers, which lack either molecular recognition ability or switchable imprinted networks, this unique insulin delivery system was composed of tunable and low crosslinked imprinted networks, which thereby enabled better self-regulation of insulin delivery. Copyright © 2010 VBRI press.