When Kawasaki introduced the ZX-6R back in 1995, it was the first middleweight sport bike, since the 1992 GSXR600 with an aluminum frame. It had a dry weight of 401.2 lb (182.0 kg), wet weight of 454 lb (206 kg), and was capable of accelerating 0 to 60 mph (0 to 97 km/h) in only 3.6 seconds.

With competition from Honda's CBR600F4i, Suzuki's GSX-R600, and Yamaha's YZF-R6 getting more aggressive, Kawasaki decided to make an unusual move for the 2003 model year. They increased the capacity of the traditional 600 cc (37 cu in) motor to 636 cc (38.8 cu in). For riders who needed bikes for displacement-restricted racing, Kawasaki also made available a limited production 599 cc (36.6 cu in) version called the Ninja ZX-6RR, but the 636 cubic centimetres (38.8 cu in) ZX-6R would be their main mass production middleweight sport bike.

In 2005, Kawasaki again revamped the ZX-6R. Engine speed increased again by 1,000 rpm resulting in 113 hp (84 kW) at 12250 rpm. The frame and swingarm were updated, but the main changes from its predecessor lay in the design. The aluminum frame was now painted flat black, fairings were more round, and integrated turn signals were used (euro model). The exhaust was now centrally under the seat (a configuration commonly referred to as an undertail exhaust). Most of these changes were mirrored in the 599 cc ZX-6RR. For the second year in a row, the ZX-6RR again won the Supersport category award for Masterbike 2005 and placed third overall. The bike carried over to the 2006 model year with minor suspension changes and new color schemes.

For 2009, Kawasaki dramatically changed the appearance of the ZX-6R to match the more angular look of the ZX-10R. The frame was lightened albeit with the same basic construction resulting in 191 kg (420 lb) wet as opposed to 205 kg (450 lb) in 2008. Kawasaki claims the new ZX-6R is 10 kg lighter than the previous model. The greatest changes for 2009 were the redesign of the exhaust, now carried low and not requiring the thick under-seat construction of 2008 and especially the introduction of the BPF (Big Piston Fork) suspension from SHOWA for a more progressive brake-dive. The 2010 ZX-6R is changing once more with an improved engine and slipper clutch. The exhaust pre-chamber has more space and also limits exhaust noise giving the rider a smoother ride. New double bore intake funnels features two available heights which gives performance upgrades in both high and low engine speeds. The front seat is now lower.

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