Newly synthetic autotetraploid rice shows lower pollen fertility and seed setting rate relative to diploid rice, which hinders its domestication and breeding. In this study, cytological analysis showed that at meiosis I stage, an unbalanced segregation of homologous chromosomes, occurred as well as an early degeneration of tapetal cells in autotetraploid rice. We identified 941 differentially expressed proteins (DEPs) in anthers (meiosis I), including 489 upregulated and 452 downregulated proteins. The DEPs identified were related to post-translational modifications such as protein ubiquitination. These modifications are related to chromatin remodeling and homologous recombination abnormalities during meiosis. In addition, proteins related to the pentose phosphate pathway (BGIOSGA016558, BGIOSGA022166, and BGIOSGA028743) were downregulated. This may be related to the failure of autotetraploid rice to provide the energy needed for cell development after polyploidization, which then ultimately leads to the early degradation of the tapetum. Moreover, we also found that proteins (BGIOSGA017346 and BGIOSGA027368) related to glutenin degradation were upregulated, indicating that a large loss of glutenin cannot provide nutrition for the development of tapetum, resulting in early degradation of tapetum. Taken together, these evidences may help to understand the differences in anther development between diploid and autotetraploid rice during meiosis.