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公元265年,晋武帝司马炎继承其父司马昭的晋王之位,数月后迫使魏元帝曹奂将帝位禅让给他,定国号晋,建都洛阳。晋武帝即位后,大封宗室、继承了两汉的封国制。279年,司马炎命杜预、王浚等人分兵伐吴,280年灭吴,统一全国。晋武帝之子司马衷近乎白痴,群臣多主张立齐王司马攸为皇位继承人,而晋武帝固执己见一心想让其子司马衷即位,遂于283年逼死了齐王司马攸。
公元290年,晋武帝死,子晋惠帝司马衷即位,武帝死后,外戚杨骏和杨太后,父女合谋,掌握了朝廷大权。惠帝是一个近乎白痴的庸人,而其皇后贾南风怀有政治野心,并手段毒辣。291年三月,贾后联络楚王司马玮,杀了杨峻及其家属和党羽数千人,命汝南王司马亮与太保卫瓘共录尚书事以辅政,楚王司马玮为卫将军,领北军(守卫京城的禁军)中侯。从此,贾后把持朝纲,为所欲为,同年三月,司马繇密谋废除她,却反被贾后罢官职、废王号。291年六月,贾南风诬告汝南王亮与卫瓘图谋不轨,让惠帝给楚王玮下诏,命他将汝南王亮与卫瓘等人免官。楚王玮接到密诏,借机发泄私怨,连夜派兵包围了二人的府第,汝南王被杀。不久,贾后又以惠帝的手诏,责楚王司马玮擅杀大臣,杀司马玮。至此,朝廷权力都落在贾南风手里。贾后以贾模为散骑常侍,加侍中;安南将军裴楷为中书令,加侍中,共掌机要。299年末,贾后将皇太子司马遹废为庶人,又将其毒死,以便自己长期专权。300年四月,赵王司马伦在他的心腹孙秀的谋划下,宣称为太子报仇,起兵进攻洛阳,杀贾后及张华、裴頠等。301年初,司马伦自立为帝。与此同时,齐王司马冏、河间王司马颙、成都王司马颖,拥兵各据一方。301年三月,齐王司马冏与豫州刺史何勖、龙骧将军董艾等起兵共同讨伐赵王伦,并派遣使者约请成都王颖,河间王颙等发兵,诸王先后响应。四月,洛阳城中卫将军王舆与广陵公凗发动兵变,自南掖门入宫,杀了孙秀及其党徒,囚禁了赵王伦,不久赵王司马伦被杀。晋惠帝复位,齐王司马冏辅政。惠帝无子,按亲疏顺序应由成都王司马颖为皇太弟。齐王冏贪恋权位,立了惠帝一个侄子司马覃为皇太子,引起成都王颖的不满。302年,河间王颙推尊成都王颖为首,起兵讨冏,骠骑将军长沙王司马乂起兵为内应,发兵攻司马冏,司马冏兵败被杀。齐王冏死后,长沙王乂(“开朗果断,才力绝人,虚心下士”) 入掌朝柄,与河间王颙、成都王颖间嫌隙渐生。303年七月,颙、颖联合起兵讨伐司马乂,颙命张方率军七万,自函谷关东攻洛阳;颖派陆机等将兵二十万南向洛阳,战久,司马乂粮乏,东海王司马越秘密与殿中诸将联合逮捕了司马乂,次年初司马乂为司马颙部将所杀。304年,成都王司马颖进占洛阳后,把持朝政。同年三月,废司马乂所立皇后羊献容,废皇太子司马覃,不久以皇太弟之身份都督中外诸军事。304年七月,东海王越奉惠帝诏亲征颖,为颖所败,逃归东海。同月,幽州刺史王浚联合并州刺史司马腾起兵讨伐司马颖,司马颖以匈奴贵族刘渊为北单于,参丞相军事,发匈奴人抗浚、腾军,刘渊遂乘机起兵反晋,旋即拥众五万。王浚与司马腾连破颖军,邺中大震,司马颖仓惶挟惠帝奔洛阳,返洛阳后司马颖军政权被夺,大权落入张方之手。304年十一月,张方挟持惠帝和司马颖、司马炽等西迁长安,次月,诏司马炽代司马颖为皇太弟。遥以司马越为太傅(越辞不受),与顒夹辅帝室,这时朝政大权转入河间王司马颙手中。305年,东海王司马越以迎惠帝为名,起兵讨伐河间王司马颙。306年,司马颙败,司马越迎惠帝还洛阳。成都王司马颖北渡河为人所杀,河间王司马颙后来在应诏赴洛阳途中为人所杀。
公元306年,惠帝中毒死,皇太弟晋怀帝司马炽即立,朝政大权落入东海王越之手。经过这次变乱,西晋的统治机能从此瘫痪。308年,刘渊改称皇帝,建都平阳,国号汉。310年刘渊死,子刘和立。刘渊死时,受顾命之托的刘聪握十万劲卒,刘和发兵要消灭刘聪,反为刘聪所杀,刘聪即帝位。311年三月,司马越病死。311年五月,刘聪攻陷洛阳,晋王公百官及百姓死者三万多人,晋怀帝被虏到平阳。晋怀帝被虏后,晋人立憨帝于长安。公元316年,刘聪遣刘曜攻长安,晋愍帝出降,西晋亡。怀、愍两帝在平阳受尽侮辱,最后都为刘聪所杀。
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