Grain filling is a pivotal grain weight determinant factor and has a great impact on rice yield potential. High grain weight was attributed to a high grain-filling rate. Proteomic analysis during the early ripening stage of rice grains from two cultivars that possess contrasting phenotypes in grain-filling rates was performed to identify proteins associated with high grain-filling rates. Two hundred and nineteen differentially expressed proteins (DEPs) were identified from the grain of two selected cultivars. We observed six more abundant enzymes involved in starch and sucrose metabolism during rice grain filling in the high grain-filling rate cultivar X42. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that most of the identified DEPs during grain filling were implicated in physiological and biochemical processes. These processes include carbohydrate metabolism, energy metabolism, secondary metabolites metabolism, and amino acids metabolism. Besides, most of those identified DEPs are differentially expressed in the two rice cultivars during grain filling. These findings indicate the essential roles of DEPs in rice grain development. During the grain-filling stage, starch, sucrose, fatty acids, and amino acids biosynthesis were more active and their metabolisms were also significantly enriched. Protein–protein interactions indicate the implication of proteins in several biological processes, for instance, carbohydrate metabolism, fatty acid metabolism, energy metabolism, and secondary metabolites biosynthesis. Data from our study provided valuable information about carbohydrate and amino acids biosynthesis, transport, and their metabolism in two genotypically grain filling.