Euphohyrisnoids A (1) and B (2), two highly rearranged lathyrane diterpenoids featuring a unique tetracyclo[10.2.2.01,10.03,7]cetane and tricyclo[8.4.1.03,7]pentadecane skeleton, respectively, were isolated from the seeds of Euphorbia lathyris. Their structures were determined by detailed spectroscopic analysis and were further confirmed by single-crystal X-ray diffraction. 1 significantly inhibited adipogenesis in 3T3-L1 adipocytes by retarding cell differentiation at the early stage.