Etherification of glycerol by isobutylene was performed using ion-exchange resin Amberlyst 15, partially neutralized Amberlyst 15 as heterogeneous catalyst, and p-toluenesulfonic acid as a homogeneous catalyst. Amberlyst 15 exhibited strong internal diffusion limitations for the initial composition of reaction mixture. Diffusion limitations decrease in the course of reaction due to the accumulation of mono-ether having excellent solubilizing properties. Oligomerized isobutylene is a dominant by-product for high isobutylene-to-glycerol ratio and long contact time in the case of Amberlyst 15. Density reduction of acidic protons in Amberlyst 15 by partial ion exchange with sodium ions leads to considerable reduction of isobutylene affinity to Amberlyst 15, and as a result, it reduced losses of isobutylene. This partial neutralization leads to lower space-time yields of target products, but enhances selectivity to higher ethers with maintaining conversion of glycerol over 95%.