Gary Sheffield also left in the sixth inning after appearing to aggravate his right hamstring issues following a single to left-center, but he walked off under his own power.
Niese had to stretch to receive a throw while covering first base on a potential 3-6-1 double play. He went into a split, however, missing the bag in the process. With manager Jerry Manuel and the training staff on the mound, Niese then collapsed in pain as he tried to throw a practice pitch. The young left-hander was helped off the field and into the clubhouse, declining to put any weight on that right leg.
Niese finished the day having allowed one hit and one walk in 1 2/3 innings. Eighteen of his 28 pitches were for strikes, and he departed with a 2-0 lead, replaced by Nelson Figueroa, who only lasted 1 2/3 innings as a spot starter on Monday against the Diamondbacks.
Figueroa connected on a two-run triple in the bottom of the second inning to put the Mets on top by a 4-0 score.
Niese (1-1) had pitched well in his second callup to the Majors this season, pitching into the seventh inning in both of his previous starts. The southpaw had been on a roll for Triple-A Buffalo, winning seven straight starts after an 0-6 start to the year, when he was called up to replace the injured Fernando Nieve.
Niese is the fourth Mets starter to suffer an injury this season, joining Nieve, John Maine and Oliver Perez. Perez missed roughly two months with patella tendinitis in his right knee before rejoining the rotation in July. Maine, meanwhile, has not pitched since the first week of June with weakness in his right shoulder.
That's all in addition to the loss of setup man J.J. Putz and key position players such as Carlos Delgado, Jose Reyes and Carlos Beltran.
Tim Britton is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.