In the present study, pore adsorption behavior of globular myoglobin (Mb) at mesoporous silicas was examined utilizing the low-temperature differential scanning calorimetry (DSC) method. The DSC method relies on a decrease in heat of fusion for the pore water upon adsorption of Mb. The amount and structure of Mb adsorbed into the mesoporous silica were examined by DSC and optical absorption spectroscopy. The results indicated that the pore adsorption behavior of Mb strongly depended on the solution pH and pore size of mesoporous silica. For the adsorption of Mb (diameter = 3.5 nm) into mesoporous silica with narrow pores (pore diameter = 3.3 nm) at a pH ranging from 7.0 to 3.7, the penetration of both folded and denatured Mb molecules was confirmed. The folded Mb could penetrate into large mesoporous silica pores (pore diameter = 5.3 and 7.9 nm), whereas the penetration of the denatured Mb molecules was completely inhibited. The distribution of folded Mb at mesoporous silica depended on the pore size; almost all folded Mb molecules located inside mesoporous silica pores of diameters 3.3 and 5.3 nm, whereas the Mb molecules distributed at bot internal and external pore surfaces of mesoporous silica with 7.9 nm in pore diameter. These pore adsorption behaviors suggest that aggregation or stacking of the Mb molecules at the pore entrance regions of the large pores affected the pore adsorption behavior.