There is lack of thermodynamic studies to describe the LE-LC 2D-phase transition of dipalmitoyl phosphatidyl glycerol (DPPG) although it is one of the main components of lung surfactants. Spread monolayers of synthetic DPPG are investigated in a broad temperature range on subphases modeling the native biological substrate. The phase transition pressure changes linearly with temperature, which confirms the principal applicability of the two-dimensional Clausius-Clapeyron equation to evaluate thermodynamic data of such systems. Brewster angle microscopy performed at monolayer compression shows that it is strongly heterogeneous during phase transition. The competition between strong condensation effects of Ca2+ cations on the negatively charged DPPG anions and electrostatic repulsion due to Na+ ions preventing condensation leads to a very fast growth of the LC phase. As a consequence, strong irregularities in the domain shapes and size distribution are observed. A new approach is proposed to determine the molar area at the phase transition from the set of pi/A isotherms recorded at different temperatures. The two-dimensional Maxwell relation and Clausius-Clapeyron equation were simultaneously applied to calculate the required parameters with a reasonable accuracy. The entropy changes at the phase transition, transition heats, and the critical temperature are calculated.