Hydroxyethyl starch (HES) solutions, widely used plasma substitutes, reportedly attenuate capillary leakage via physical plugging of capillary defects. We investigated how 2% HES solutions of different molecular weights (HES70: 70 kDa, HES130: 130 kDa, HES200: 200 kDa, and HES670: 670 kDa) affect dye release from polyacrylamide gels (PAGs) as a model of endothelial glycocalyx. We assessed dye release from 4% PAG with varying concentrations of albumin [0, 1, 2, 4, and 8% (w/v)] by measuring the change in dye absorbance (ΔAbs) at 5 h for each HES solution. For PAG containing no albumin, ΔAbs for HES130 was 30% lower than that for HES70 and HES200, and 50% lower than that for HES670. At concentrations of 1–8% albumin, ΔAbs at 5 h with HES70, HES130, and HES200 solutions were almost half that with the HES670 solution, but no significant differences were noted in ΔAbs at 5 h among HES70, HES130, and HES200 solutions. The inhibition of dye release by HES670 is likely due to the hindering effect of HES molecules partitioned into gel pores. However, a unique property of HES130, including the heavy hydroxyethylation at the C2 position, may promote specific interactions with PAG and thereby inhibit solute release. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 85–90, 2013.